Long-term supplementation with melatonin delays reproductive senescence in rats, without an effect on number of primordial follicles.

The primary objective of the present experiment was to determine if lifelong supplementation with melatonin delayed reproductive senescence through decreased loss of ovarian primordial follicles. Holtzman rats were divided into three treatments on Day 10 after pupping (Day 0 = day of pupping). Treatment 1 pups had access to water, whereas Treatment 2 and 3 pups had access to water containing 10 microg/ml melatonin only at night (Treatment 2) or continuously (Treatment 3). Estrous cycles and weights of pups were monitored at selected times during the experiment; ovaries were removed for histology at 75 and 380 days of age. Vaginal opening in Treatment 2 was delayed (P <.01) compared with Treatments 1 and 3, but there was no difference (P > 0.05) among treatments in percentage of normal length estrous cycles from vaginal opening to 75 days of age. There were fewer (P < 0.001) abnormal-length estrous cycles from 180 to 380 days of age in Treatment 2 as compared with Treatments 1 or 3. There was no effect of treatment (P > 0.05) on number of primordial follicles. In conclusion, nighttime, but not continuous supplementation with melatonin, delayed puberty and reproductive senescence without any effect on number of primordial follicles.